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(6d) Scale-up Effects On the Growth Kinetics in High-Shear Wet Granulation: a Case Study

Cavinato, M., University of Padua
Bresciani, M., GlaxoSmithKline
Pignatone, I., GlaxoSmithKline
Bellazzi, G., GlaxoSmithKline
Canu, P., University of Padua
Santomaso, A. C., University of Padua
Artoni, R., University of Padua

Scale-up of high-shear wet granulators is currently difficult to perform and there are no universally applicable scale-up rules. It is not completely clear how changes in granulator geometry and processing conditions can affect the granule growth [1]. An investigation on the scale-up effects on the growth behaviour in high-shear wet granulation is here described. Firstly, a mixture of some common-used pharmaceutical powders was processed using a top-driven, small scale granulator (2 l vessel volume). The processing conditions were systematically changed in order to arrange reproducible liquid dispersion conditions and nucleation regimes [2]. Secondly, the same powder mixture was processed using a pilot plant scale, bottom-driven granulator (65 l vessel volume). The dimensionless spray flux concept was used in order to keep the same liquid dispersion conditions [2]. The Focused Beam Reflectance Measurement Probe (FBRM) was used in combination with other particle size distribution measurement techniques (e.g. sieve analysis, laser diffraction methods) in order to carry out a detailed analysis of the growth behaviour. As already demonstrated by Cavinato et al. [3], this technique presents a good degree of accuracy and reproducibility. Results clearly showed the effect of the change in the granulator geometry and scale on the liquid distribution and, thus, the growth kinetics. A modification of the dimensionless spray flux number was furthermore proposed in order to best describe the phenomena and improve the predictability of the method.

[1] P. R. Mort, Scale-up of binder agglomeration processes, Powder Technology 150 (2005) 86-103. [2] J.D. Litster, K.P. Hapgood, J.N. Michaels, A. Sims, M. Roberts, S.K. Kameneni, T. Hsu, Liquid distribution in wet granulation: dimensionless spray flux, Powder Technology 114 (2001) 32?39. [3] M. Cavinato, D. Kayrak-Talay, J.D. Litster, Predicting the growth kinetics based on the formulation properties in high shear wet granulation, World Congress on Particle Technology, Nuremberg 25-29 April 2010.